The National Institutes of Health estimates that 30 million American men suffer from mild, moderate or complete erectile dysfunction. Erectile dysfunction is the chronic (greater than three months duration) inability to maintain a penile erection sufficient to achieve penetration of one's sexual partner, complete sexual intercourse and/or achieve sexual satisfaction.
Most causes of erectile dysfunction have an adverse effect on nerves and/or blood vessels to, from, and within the penis. Causes of erectile dysfunction include: atherosclerosis (thickening, narrowing, hardening and less elasticity of penile blood vessels); breakdown of a chemical message to or within the penis thereby preventing the erectile chambers from becoming engorged with blood to produce an erection; venous leakage (blood seeps out of the penile vessels instead of being trapped inside during an erection); nerve and blood vessel damage caused by diabetes; nerve damage caused by degenerative diseases such as multiple sclerosis and Parkinson's disease; nerve damage caused by surgical removal of prostate, bladder or rectum to treat cancer or other disease processes; abdominal aortic aneurysm (penile nerves and vessels may be damaged); B-12 deficiency (causes neurological problems throughout the body); radiation treatments for prostate, bladder and/or rectal cancer; psychological factors (stress, depression, performance anxiety); hormonal imbalances such as testosterone deficiency and/or abnormally high level of prolactin causing decreased libido (sexual desire); alcohol; tobacco useage; substance abuse; Peyronie's disease (penile connective tissue thickens thereby interfering with the ability to have an erection); injury to any nerves or arteries necessary to have an erection (pelvic fracture, brain, spinal cord, abdomen or penis); antihypertensives; antidepressants; tranquilizers; antifungals; antacids; cholesterol-lowering drugs; diuretics; nitrates; Proscar (medication for benign prostate hyperplasia); propecia (to counteract baldness); estrogens; antiandrogens; antihistimines; anticholinergics; anticancer drugs; aging, hypertension; obesity; hyper-cholesterolemia.
Known patents include:
U.S. Pat. No. 6,436,944 to Maytom.
U.S. Pat. No. 6,589,990 to Kanakaris et al.
U.S. Pat. No. 6,548,544 to Adaikan et al.
U.S. Pat. No. 6,414,027 to Neal.
U.S. Pat. No. 6,398,720 to Dabal.
U.S. Pat. No. 6,376,554 to Cheetham et al.
VIAGRA®(sildenafil citrate, Pfizer, Inc., New York, N.Y.), taken orally, is effective for up to 80% (depending upon the severity of erectile dysfunction (ED) and/or any underlying disease) of patients to produce an adequate erection for sexual intercourse. It is effective for a broad range of causes. Successful VIAGRA® patients have normal, natural erections. VIAGRA® has no effect on libido (sexual desire) so that it will not be effective unless a man feels stimulated.
When a man feels sexually stimulated, a chemical message in the penis causes the smooth muscle (lining the penile arteries) to relax so that these arteries dilate (widen) causing the two erectile chambers (corpora cavernosa) to become engorged with blood to produce an erection.
As a man ages, these chemical messages can be broken down by an enzyme in the penile tissues, causing erectile dysfunction. VIAGRA® prevents the breakdown of these chemical messages by suppressing the enzyme.
VIAGRA® suppresses the enzyme (phosphodiesterase) so that the erection-producing chemical cylic guanosine monophosphate (cGMP) is not broken down so that a normal erection occurs.
cGMP is a natural vasodilator (dilates penile arteries) which relaxes the smooth muscle of penile arteries so that the relaxed smooth muscle, in combination with normal blood pressure, causes the penile arteries to dilate so that the erectile chambers are engorged with blood to produce an erection.
VIAGRA® is effective for 80% of men with psychogenic erectile dysfunction and about half of men whose erectile dysfunction is secondary to spinal cord injury, diabetes or radical prostatectomy.
VIAGRA® has no proven effect on penile atherosclerosis, a primary cause of erectile dysfunction. VIAGRA® may be ineffective when, e.g., the degree of atherosclerosis is too large so that, after sexual stimulation, the arteries are not sufficiently elastic so that the amount of arterial dilation is inadequate so that there is an insufficient amount of blood in the erectile chambers to produce an erection satisfactory for sexual intercourse.
VIAGRA® may have side effects including but not limited to: headache, flushing, upset stomach, nasal congestion, urinary tract infections, color tinge to vision, increased sensitivity to light, blurred vision, bloodshot or burning eyes, diarrhea, dizziness, rash, and, rarely, priapism (a painful, prolonged erection lasting more than four hours).
Men who cannot take VIAGRA® or find it ineffective are often able to achieve erections by using another treatment which produces erections directly, without sexual stimulation. This treatment uses vasodilation (vessel dilation) by means of medications (vasodilators) which dilate the penile arteries so that the erectile chambers become engorged with blood to produce an erection. These medications relax the smooth muscle of penile arteries to cause arterial dilation.
The most common vasodilator is ALPROSTADIL® (Caverjet, Edex, Schwarz Pharma USA Holdings, Inc., Wilmington, Del.). It can be injected into the base of the penis (into one of the corpora cavernosa) with a needle or inserted into the urethra in pellet form through a delivery system calls MUSE (Medicated Urethral Suppository for Erection). ALPROSTADIL® is effective in over 80% of patients and MUSE for about 30% of men with erectile dysfunction. For men for whom ALPROSTADIL® is ineffective, an injected mixture of vasodilators (TRIMIX) is effective for about 62% of patients.
The side effects of injected ALPROSTADIL® are penile pain, bruising, scarring, priapism (a painful, prolonged erection) and decreased blood pressure. The side effects of MUSE are urethral burning, dizziness and decreased blood pressure. The effective lowest dose minimizes side effects for injections and MUSE.
Since vasodilators cause erections directly, without sexual stimulation, by dilating penile arteries, they may be effective, such as when the penile neurovascular bundles are no longer intact; e.g., when VIAGRA® is ineffective.
A non-invasive treatment for erectile dysfunction is the hand-held vacuum pump (Vacuum Erection Device, Osbon Medical Systems). A plastic cylinder (connected to the pump) is placed over the penis and a partial vacuum is quickly achieved, after pumping several times, which draws blood into the penis thereby dilating the vessels to achieve an artificial erection. A rubber constricting ring is placed temporarily at the base of the penis to prevent blood from escaping from the penis. The constricting ring may remain in place for not more than thirty minutes or damage to the penis may result.
Men who are able to achieve a normal erection but cannot sustain it because they have venous leakage may be helped by a penile constriction band. This is a ring-like device that is fastened around the base of the penis to keep blood from escaping. A penile band called Actis is available (Vivus Corp.).
When other therapies are ineffective, surgical implants may be considered. One device consists of two silicone rods implanted in the penis. The penis is permanently erect and can be pointed down along the thigh or up toward the abdomen to conceal it under clothing.
Another type of implant consists of two inflatable cylinders put into the corpora cavernosa which produce an erection when filled with saline fluid. The fluid is pumped from a reservoir implanted in the space of retsius and then fluid is transferred to the penile cylinders when an erection is desired.
A new medication Uprima (apomorphine), taken orally, is under study. It seeks to target mechanisms in the brain to produce an erection. It has been approved in Europe for treatment of erectile dysfunction.
A topical medication Topiglan (ALPROSTADIL®), under study, has had promising results, applied to the head of the penis to produce an ereciton directly, without sexual stimulation. An ointment would ease the mode of delivery while reducing the risk of adverse effects compared to injection or urethral pellet.
Two oral medications, awaiting FDA approval, are vardenafil and tadalafil. They, like sildenafil (VIAGRA®) are PDE-5 inhibitors which suppress the enzyme which breaks down the natural vasodilator cGMP in order to facilitate and maintain an erection.
When two or more medications are used in combination, the treatment is called combination pharmacotherapy. When a medication is used alone, the treatment is called monotherapy. When any monotherapy fails, a combination pharmacotherapy may be effective.
Combination pharmacotherapies using at least two medications have been used experimentally with significant results. The combination of VIAGRA® and MUSE has been evaluated (Eur. Urol. 2000; 38: 30–4 and BJU. Int. 2000; 86: 469–73 and Urol. 2000; 163: 198).
Another study evaluated the benefit of oral alpha blockers (daily oral doxazosin) in combination with intracavernosal (injected) ALPROSTADIL®(Urol. 1998; 52: 739–43).
Another study (Internat. J. Impot. Res. 2002; 14(1): 50–53) combines VIAGRA® with daily oral Cardura (doxazosin).
Two ALPROSTADIL® studies are described in Prostate Disorders, The Johns Hopkins White Papers, 2002, p. 57. Scientists hypothesized that regular (periodic) injections of vasodilators, independent of sexual activity, might help bring about the return of normal, natural erections. In a small 12-week study, 67% of radical prostatectomy patients regularly injected with ALPROSTADIL® eventually achieved normal, natural erections, compared to 20% of those who did not receive injections. Other results were also reported in a one year study (Urology, 2001; 57 (3)), not cited in the White Papers.
A study set forth in the above-described Johns Hopkins White papers of 270 radical prostatectomy patients regularly (periodically) receiving MUSE (ALPROSTADIL® by urethral pellet), independent of sexual activity, showed that this treatment may be successful in achieving normal, natural erections in 40% of cases.